Figure 4. The intramitochondrial signaling pathways.

The pathways leading to mitoK_ATP opening, ROS production, and MPT inhibition are shown. Signals arising from Gi-coupled receptors are delivered to mitochondria via the terminal kinase PKG. Signals arising from ouabain action upon the Na-K ATPase are delivered to mitochondria via two terminal kinases, PKCε and Src. The terminal kinases are localized in the signalosomes. PKG phosphorylates an unknown MOM receptor, “R1”, whereas PKCε and Src act in conjunction to activate a distinct MOM receptor, “R2”. These MOM receptors transmit the signal by an unknown mechanism to PKCε1 located at the inner membrane. The activated PKCε1 phosphorylates and opens mitoK_ATP. PKCε1 activity is likely to be counteracted physiologically by Ser/Thr protein phosphatases (PPase) such as PP2A. MitoK_ATP opening via PKCε1 or by K_ATP channel openers such as diazoxide causes K⁺uptake, increased matrix pH, and increased H₂O₂ production from Complexl. H₂O₂ produced by mitoK_ATP activity now diffuses and activates both PKCε1 and PKCε2. PKCε2 inhibits MPT, thus reducing cell necrosis and infarct size. The figure is from Costa and Garlid [32].